Pharmacokinetics of Sulfadimethoxine and Sulfamethoxazole in Combination with Trimethoprim after Oral Single- and Multiple-Dose Administration to Healthy Pigs |
| |
Authors: | Mengelers MJB van Gogh ER Huveneers MBM Hougee PE Kuiper HA Pijpers A Verheijden JHM van Miert ASJPAM |
| |
Institution: | (1) Department of Toxicology, Wageningen, The Netherlands;(2) Department of Farm Animal Health, Division of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, PO Box 80152, NL-3508 TD Utrecht, The Netherlands;(3) Division of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, PO Box 80152, NL-3508 TD Utrecht, The Netherlands |
| |
Abstract: | The pharmacokinetics were studied of sulfadimethoxine (SDM) or sulfamethoxazole (SMX) in combination with trimethoprim (TMP) administered as a single oral dose (25 mg + 5 mg per kg body weight) to two groups of 6 healthy pigs. The elimination half-lives of SMX and TMP were quite similar (2–3 h); SDM had a relatively long half-life of 13 h. Both sulfonamides (S) were exclusively metabolized to N4-acetyl derivatives but to different extents. The main metabolic pathway for TMP was O-demethylation and subsequent conjugation. In addition, the plasma concentrations of these drugs and their main metabolites after medication with different in-feed concentrations were determined. The drug (S:TMP) concentrations in the feed were 250:50, 500:100, and 1000:200 mg per kg. Steady-state concentrations were achieved within 48 h of feed medication, twice daily (SDM+TMP) or three times a day (SMX+TMP). Protein binding of SDM and its metabolite was high (>93%), whereas SMX, TMP and their metabolites showed moderate binding (48–75%). Feed medication with 500 ppm sulfonamide combined with 100 ppm TMP provided minimum steady-state plasma concentrations (C
ss,min) higher than the concentration required for inhibition of the growth of 90% of Actinobacillus pleuropneumoniae strains (n = 20). |
| |
Keywords: | in-feed medication metabolites pharmacokinetics pigs protein binding sulfonamides trimethoprim |
本文献已被 PubMed SpringerLink 等数据库收录! |
|